Possible association between thyroid autoimmunity and Menière's disease

Various aetiopathological mechanisms have been postulated to be at the root of Menière's disease (MD), and some data suggest that there may be also an underlying autoimmune factor. In fact, Menière patients manifest certain characteristics that are typical of autoimmune involvement association of particular human leucocyte antigen haplotypes, the presence of antibodies against internal ear antigens. In this study, we evaluated the association between thyroid autoimmunity and MD in a non-selected group of patients. We recruited 50 consecutive MD patients and two groups as controls: group A, 82 healthy volunteers; and group B, 50 subjects suffering from acute unilateral peripheral vestibulopathy. All subjects were submitted to instrumental assessment of cochlear-vestibular function and analysis of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, anti-TSH receptor antibody (TR-Ab), anti-thyroperoxidase antibody (TPO-Ab) and anti-thyroglobulin antibody (Tg-Ab) in the blood. The prevalence of autoimmune thyroiditis in group B [6/50 (12%); 66.7% TPO-Ab and 33.3% Tg-Ab] was superimposable with the healthy controls [6/82 (7%); 66.7% TPO-Ab and 33.3% Tg-Ab]. In contrast, 38% of the MD patients (P = 0.0001 versus group A and group B) had significant autoantibody levels (68.4% TPO-Ab; 15.8% TPO-Ab + TR-Ab; 10.5% Tg-Ab; 5.2% TPO-Ab + Tg-Ab). Furthermore, 14% of the MD patients were hyperthyroid under l-thyroxine therapy, while no dysfunction was seen in the control groups. Overall, our data demonstrate a significant association between MD and thyroid autoimmunity, which suggests that an autoimmune factor is involved in the aetiopathogenesis of this disease. These findings suggest that it should be useful to submit MD patients to multi-disciplinary clinical investigation.     

Visual processing in patients with Frégoli syndrome

We investigated four paranoid schizophrenic patients diagnosed with Frégoli delusion, and four matched psychotic controls. Neuropsychological testing included visual and verbal recognition memory, in addition to a comparison of left and right hemispheric processing of two different classes of stimuli, animate and inanimate objects. Performance on the recognition memory test failed to discriminate between the two psychotic groups on the basis of facial recognition, however, the patients with Frégoli delusion failed to show the right hemisphere processing advantage for the animate class of stimuli found for the set of norms and also present in the psychotic control group. These results are discussed in the context of both current theories of the delusional misidentification syndromes in general, and models of facial recognition in particular.     

Measurement of platelet membrane fluidity in patients with Binswanger's disease or Alzheimer's disease

目的和方法：探讨血小板在Ｂｉｎｓｗａｎｇｅｒ病（ＢＤ）发病中的作用，用荧光探针测定１１例ＢＤ患者、９例Ａｌｚｈｅｉｍｅｒ病（ＡＤ）患者和６例健康对照者血小板膜的流动性（ＰＭＦ），以颈内静脉和肘静脉血ＰＭＦ的差值作为反映脑循环中ＰＭＦ变化的指标。结果：ＢＤ和ＡＤ患者的ＰＭＦ的均值显著低于健康对照组，但只有ＢＤ患者颈内静脉血ＰＭＦ显著低于肘静脉血，ＢＤ患者ＰＭＦ差值与ＨＤＳ积分具有显著相关。结论：ＢＤ病人脑循环中ＰＭＦ降低可能是ＢＤ的发病因素之一。     

Segment difficulty in two-stroke movements in patients with Parkinson’s disease

In the horizontal plane on a digitizer tablet, subjects made an elbow-extension, two-stroke movement away from the trunk to a first target and then on to a second target. If the two segments of the movement were executed in an integrative manner, the accuracy constraint on the first segment should have produced changes in kinematic features not only of that segment but also of the second segment. Two-stroke movements of ten Parkinson's disease (PD) patients and ten controls were studied to examine whether a high-accuracy constraint on the first segment influences the performance of the second, when the second target has either a high- or low-accuracy requirement. When the accuracy requirement of the second segment was low, both PD patients and controls showed that changing the first target size from large to small influenced the performance of not only the first segment but also the second segment. For the first segment, movement time, acceleration time, and deceleration time increased when moving to the small first target as compared to the large first target. The peak velocity and peak acceleration also decreased as the first target size decreased. For the second segment, similar patterns of kinematic changes in relation to the first segment were observed in all of these parameters. When the accuracy requirement of the second segment was high, the controls showed similar changes in the first and second segments in relation to the change of first target sizes. In contrast, the PD patients showed that the target size that defined the first movement mainly influenced the performance of that segment. Among kinematic parameters tested for the second segment, only acceleration time increased as the first target size decreased. Other parameters in general did not change, regardless of whether movement of the first segment was made to the small or large target. These results indicate that the two-stroke movements of PD patients showed little evidence that they were planned and organized in an integrative manner when there was a high-accuracy constraint imposed on the second segment. On the other hand, control subjects performed two-stroke movements in a manner that suggested the two segments were planned and organized together regardless of an accuracy constraint imposed.     

Assessment of postural instability in patients with Parkinson’s disease

Postural instability is one of the most disabling features of idiopathic Parkinson’s disease (PD). In this study, we focused on postural instability as the main factor predisposing parkinsonians to falls. For this purpose, changes in sway characteristics during quiet stance due to visual feedback exclusion were studied. We searched for postural sway measures that could be potential discriminators for an increased fall risk. A group of 110 subjects: 55 parkinsonians (Hoehn and Yahr: 1–3), and 55 age-matched healthy volunteers participated in the experiment. Their spontaneous sway characteristics while standing quiet with eyes open and eyes closed were analyzed. We found that an increased mediolateral sway and sway area while standing with eyes closed are characteristic of parkinsonian postural instability and may serve to quantify well a tendency to fall. These sway indices significantly correlated with disease severity rated both by the Hoehn and Yahr scale as well as by the Motor Section of the UPDRS. A forward shift of a mean COP position in parkinsonians which reflects their flexed posture was also significantly greater to compare with the elderly subjects and exhibited a high sensitivity to visual conditions. Both groups of postural sway abnormalities identified here may be used as accessible and reliable measures which allow for quantitative assessment of postural instability in Parkinson’s disease.     

IL-10 genotype analysis in patients with Behçet's disease

Beh?et's disease (BD) is a multisystem inflammatory disease characterized by recurrent orogenital ulceration, ocular inflammation, and skin lesions. The etiology of the disease is currently unknown but evidence suggests that there is a strong genetic component mediating the chronicity of the disorder. We have examined the association between polymorphisms at position -1082, and -819 in the promoter region of the gene encoding IL-10 in patients with Beh?et's disease from two distinct patient populations. The IL-10 -1082AA genotype was weakly associated with BD when all patients were analyzed as a group (pc = 0.04, OR 1.4, 95% CI 1.1-1.9), but not in the UK or Middle Eastern (ME) cohorts of patients alone compared to local controls. An association with IL-10 -819T was evident in all BD patients, (pc = 0.02, OR 1.5, 95% CI 1.1-2.0), and this was because of an association in the UK but not ME patients (pc = 0.0004, OR 2.1, 95% CI 1.4-3.3). The -1082A/-819T haplotype, which is linked to low production of this cytokine, was not significantly associated with Beh?et's disease. This link between BD, a chronic, relapsing, autoinflammatory condition, and a genotype associated with low IL-10 production provides evidence that abnormalities in the genetic control of cytokine levels may be relevant in influencing the immune response in Beh?et's disease in some patient groups.     

Impaired inhibitory oculomotor control in patients with Parkinson’s disease

A hallmark of voluntary control is the capacity to inhibit or change partially prepared responses, an ability thought to be compromised in patients with Parkinson’s disease (PD). To test this hypothesis in relation to oculomotor control, PD patients and age-matched controls performed a redirect task in which they were instructed to cancel a partially prepared saccade on some random fraction of trials. Using a race model framework, the time it takes to cancel a saccade, the target switch reaction time (TSRT), was estimated for PD and control subjects. While saccadic reaction times of control and PD subjects were similar, the average TSRT in PD subjects was 139 ms, and was significantly greater than the TSRT in controls, which was 113 ms. These results support the hypothesis that poor voluntary control exhibited by PD patients in a variety of complex behaviors may be caused by impaired inhibitory control as a result of basal ganglia dysfunction.     

How to assess disease activity in patients with chronic urticaria?

Background:  The current EAACI/GA²LEN/EDF guidelines recommend assessing disease activity in chronic urticaria (CU) by using an established and well-defined symptom score, i.e. the urticaria activity score (UAS), which combines daily wheal numbers and pruritus intensity. However, this UAS has never been formally tested for its suitability in assessing CU activity.
Aim:  To determine the UAS correlation with quality of life (QoL) in CU patients and to compare the UAS to other symptom scores.
Methods:  Chronic urticaria symptoms (wheals, erythema, angioedema, pruritus) were assessed on seven consecutive days in 111 CU patients for their numbers, duration, size, and/or intensity. Quality of life was assessed by using the Dermatology Life Quality Index. Both, urticaria activity and QoL were determined before and after a 3-week period, in which the patients followed a pseudoallergen-low diet.
Results:  Urticaria activity score values correlated positively, albeit weakly, with QoL impairment in CU patients ( r ² = 0.31, P  < 0.05). Also, changes in QoL following a pseudoallergen-low diet were reflected by the changes observed in the UAS ( r ² = 0.30, P  < 0.05). No significant differences were found comparing the QoL correlation of the UAS and other symptom scores combining up to four CU symptom qualities. Quality of life correlation with UAS values increased with the number of days the UAS was assessed and plateaued starting from the fourth consecutive day.
Conclusions:  Our findings back the current guideline recommendations to use the UAS for monitoring disease activity in CU patients. Urticaria activity score mean values of at least four consecutive days should be used.     

Interleukin-18 promoter polymorphisms in patients with Behçet's disease

Beh?et's disease (BD) is an idiopathic systemic inflammatory disease and is considered to be a T helper 1 (Th1) type cytokine driven disorder. Moreover, levels of interleukin-18 (IL-18), a pivotal mediator of Th1 cytokine response, have been reported to be upregulated in BD. Therefore, we investigated the distribution of IL-18 promoter -607 C/A and -137 G/C polymorphisms in 103 BD patients (mean age 41.0 years; 48 male, 55 female) using allele-specific-polymerase chain reaction. As compared with healthy control subjects, BD patients had a significantly higher frequency of the -607 CC genotype (42.7% vs 23.3%, odds ratio [OR] = 2.455, 95% confidence interval [CI] = 1.350-4.461, p(c) = 0.021) and a higher frequency of the -607 C allele (60.7% vs 48.1%, OR = 1.668, 95% CI = 1.129-2.464, p = 0.0101). Haplotype analysis showed that BD patients had significantly less -607A/-137G haplotype (27.3% vs 44.2%, OR = 0.469, 95% CI = 0.268-0.820, p(c) = 0.032) and -607A/-137G haplotype homozygote (5.8% vs 20.4%, OR = 0.242, 95% CI = 0.096-0.612, p(c) = 0.014) than control subjects. In addition, the frequency of -607C/-137G haplotype homozygote was significantly higher in BD patients than control subjects (48.5% vs 20.4%, OR = 3.684, 95% CI = 1.997-6.791, p(c) = 0.0014). Although there were no associations between the polymorphisms and clinical manifestations or severity, patients with the -607 CC genotype or -607C/-137G haplotype homozygote showed significantly earlier symptom development (p = 0.034 by ANOVA; p = 0.009 by t-test, respectively) than those with other genotypes or diplotypes. These results suggest that the IL-18 promoter gene is a candidate susceptibility gene in BD patients.     

Aberrant Fas ligand expression in lymphocytes in patients with Behçet's disease

BACKGROUND: Defects in immune responses have been reported in patients with Beh?et's disease (BD). To further characterize the immune dysfunction and its contribution to the pathogenesis, we have studied Fas ligand (FasL) expression in peripheral blood lymphocytes (PBL) and mononuclear cells in the skin lesions in patients with BD. METHODS: FasL expression in PBL was studied with RT-PCR and immunoblotting with rabbit anti-human FasL antibody. We studied the expression of FasL in cryostat sections of biopsy specimens of erythema nodosum lesions from 4 patients with BD and of a genital ulcer lesion in another patient using immunohistochemical staining. Apoptotic cell death was detected with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. RESULTS: We found that FasL mRNA and FasL protein expression was detected marginally in the unstimulated PBL, and was induced upon activation in normal individuals. PBL from patients with BD exhibited an enhanced expression of FasL mRNA and FasL protein without in vitro stimulation. Moreover, mitogen stimulation failed to augment FasL expression of their lymphocytes, suggesting a dysregulation of FasL expression of PBL in patients with BD. The skin biopsy specimens revealed that cells infiltrating into skin lesions expressed FasL and there were several TUNEL staining-positive cells in the lesions, suggesting that Fas/FasL-mediated apoptosis is involved in the development of the skin lesion and thus may be associated with the pathogenesis. CONCLUSIONS: We found an excessive expression of FasL in circulating as well as skin-infiltrating lymphocytes and the presence of apoptotic cells in the skin lesions, suggesting that lymphocytes expressing FasL aberrantly may play a role in the development and pathogenesis of BD.     

Association of interleukin-1 gene polymorphisms with sudden sensorineural hearing loss and Ménière's disease

Sudden sensorineural hearing loss (SSNHL) and Ménière's disease are the most common inner ear diseases in which the causes are unknown. As recent magnetic resonance imaging has demonstrated disruption of the blood-labyrinth barrier in these inner ear diseases, inflammatory reaction associated with increased permeability of the blood vessels may be involved. The genotypes of interleukin 1A (IL1A) (-889C/T; rs1800587) and interleukin 1B (IL1B) (-511C/T; rs16944) were determined using an allele-specific primer-polymerase chain reaction method in 72 patients with SSNHL, 68 patients with Ménière's disease, and 2202 control subjects living almost in the same area as the patients. A significantly higher prevalence of the IL1A-889T allele was observed in SSNHL and Ménière's disease compared with controls, although no significant difference in distribution of IL1B-511C/T genotypes was observed between the patients and controls. Adjusted odd ratios for SSNHL and Ménière's disease risks in the -889TT genotypes were 25.89 (95% confidence interval (CI) 12.19-54.98) and 18.20 (95% CI 7.80-42.46), respectively, after age and gender were taken as moderator variables. Our results suggested that IL1A is closely associated with susceptibility of SSNHL and Ménière's disease.     

Transvaginal Doppler sonography: is there a role for this modality in the evaluation of women with postmenopausal bleeding?

OBJECTIVE: The aim of this study was to determine whether transvaginal sonography (TVS) and transvaginal Doppler sonography (TDS) can discriminate between normal and abnormal endometrium. MATERIALS AND METHODS: Patients who had vaginal bleeding an year after menopause and were not on HRT or tamoxifen were preoperatively examined by TVS and TDS on the same day of curettage. The endometrial thickness as well as the pulsatility index (PI) and resistance index (RI) of uterine arteries were recorded. RESULTS: Final pathology analysis revealed that 55/81 (67.9%) had normal endometrial tissue and 26/81 (32.1%) had an abnormality (endometrial hyperplasia, polyp or cancer). The mean endometrial thickness was greater in the abnormal group (9.4 mm versus 3.8 mm, P < 0.05). The mean PI of normal and abnormal endometrium were 2.85 and 1.53. The mean RI of normal and abnormal endometrium were 1.04 and 0.68. Univariate analysis found that PI < 2 and RI < 0.9 were correlated with abnormal endometrium (P < 0.05). Multivariate analysis revealed significance only for the endometrial thickness. CONCLUSIONS: TDS cannot distinguish between normal and abnormal endometrium. Using TVS only would result in a significant reduction of endometrial biopsy or curettage.     

Induction of autoantibodies to glutamate in patients with Alzheimer’s disease

Autoantibodies to glutamate were found in blood plasma from patients with Alzheimer’s disease. The content of autoantibodies to glutamate in blood plasma from patients with moderate and severe dementia was 2-fold higher compared to patients with mild dementia. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 2, pp. 140–141, February, 2007     

Influence of sex on patients with Behçet's disease in Korea

Behçet''s disease (BD) is a multisystemic inflammatory disorder known as having a histopathological findings of vasculitis. The influence of sexual difference on BD is a well-known fact and there are several reports suggesting a more severe course of the disease among young males. The purpose of our study was to determine the effects of gender on the severity and clinical features of BD patients in Korea. The study included 1,901 patients with BD who fulfilled the criteria of International Study Group for Behçet''s Disease or corresponded to the complete or incomplete type for the revised criteria of Behçet''s Disease Research Committee of Japan. BD in Korea showed a female predominance (M:F=0.61:1). The skin lesions were observed in 79.9% of patients, of which 77.6% had erythema nodosum-like lesion, which was more frequent in females. The ocular lesions were more common in males showing a higher frequency of uveitis. Ocular and vascular symptoms as clinical features with severe complications or mortality were more frequent in males than in females. The mean age at the onset of patients with the worst prognosis such as ocular, gastrointestinal, neurologic, and vascular involvements was significantly younger in male than in female patients (p<0.05). In conclusion, this study elucidated the influences of sexual difference on BD in Korea.     

Serum oxidant/antioxidant status in patients with Behçet's disease

The aims of this study were to assess whether the increased oxidative stress in affected tissues is reflected by serum lipid peroxidation and to check for alterations in serum levels of extracellular antioxidants and antioxidant enzyme activities in patients with Behcet's disease (BD). Serum malondialdehyde (MDA) and ceruloplasmin (Cp) levels and CuZn-superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) activities were increased, while serum transferrin (Trf) levels were diminished in patients with active ocular BD (n = 19), inactive ocular BD (n=18), and nonocular BD (n=15), compared to healthy controls (n = 20). Serum MDA levels in patients with active ocular BD and nonocular BD were significantly higher than in the inactive ocular BD group. Patients with active ocular BD also had significantly higher serum Cu-Zn SOD activities, compared to the inactive ocular BD. Erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) levels were higher in patients with active ocular BD, inactive ocular BD, and nonocular BD, compared to the control group. In addition, patients with active ocular BD and nonocular BD had significantly higher ESR and serum CRP levels, compared to the inactive ocular BD group. Serum albumin concentrations showed no significant differences among the BD patients and controls. The authors speculate that in BD patients, serum superoxide radicals may be dismutated to H2O2 by increased CuZn-SOD activity and the conversion of H2O2 to hydroxyl radical may be enhanced by iron, owing to diminished serum Trf; these mechanisms may contribute to the increased serum lipid peroxidation.     

Serum vitronectin levels in patients with Beh?et’s disease

Background/aims

To determine serum vitronectin levels in Beh?et patients with and without ocular involvement, and to evaluate the relationship between vitronectin concentrations and clinical manifestations of Beh?et’s disease (BD).

Methods

Sixty-five patients with BD and 21 control subjects were included. All patients were queried for the clinical manifestations of BD. Serum vitronectin concentrations were determined by using in vitro enzyme immunoassay kits.

Results

Serum vitronectin levels between the patients and the control subjects were not different. There was no statistically significant difference between vitronectin levels in Beh?et patients with and without ocular involvement. No correlation was found between vitronectin concentrations and clinical manifestations.

Conclusion

This is the first study evaluating vitronectin levels in Beh?et patients. Further studies involving larger numbers of subjects would be useful to improve our understanding of the functions of vitronectin in BD.     

Alpha tropomyosin as a self-antigen in patients with Behçet's disease

We report for the first time a significant increased lymphoproliferative response to alpha tropomyosin as well as observing autoantibodies to tropomyosin observed in Behcet's disease (BD) patients with posterior uveitis. Peripheral blood mononuclear cells (PBMCs) from 18 BD patients with posterior uveitis, 18 patients with other forms of noninfectious uveitis, 9 patients with retinal damage due to photocoagulation as well as 18 healthy donors were evaluated for antigen-specific lymphoproliferative responses to alpha tropomyosin and its derivative peptides. The proliferative responses of PBMCs to these antigens were studied using (3)H thymidine incorporation assay. Serum samples were also screened by ELISA for autoantibodies against tropomyosin. Six of the 18 (33%) BD patients with posterior uveitis showed increased proliferative response to alpha tropomyosin or its derivative peptides, while none of the healthy, disease controls were positive. The mean lymphoproliferative responses to tropomyosin were significantly higher (P < 0.02) in the BD patients compared to healthy or disease controls. Higher titres of anti-tropomyosin antibodies were also seen in four of the 18 BD patients but none in the healthy or disease control groups (P < 0.002). The occurrence of these abnormalities supports a possible role for alpha tropomyosin as a self-antigen in a subset of patients with Behcet's disease.     

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

Two common chronic childhood diseases-celiac disease (CD) and type 1 diabetes (T1D)-result from complex pathological mechanisms where genetic susceptibility, environmental exposure, alterations in intestinal permeability and immune responses play central roles. In this study, we investigated whether these characteristics were universal for CD independently of T1D association. For this purpose, we studied 36 children with normal small-bowel mucosa and 26 children with active CD, including 12 patients with T1D. In samples from the small-bowel mucosa, we detected the lowest expression of tight junction protein 1 (TJP1) mRNA in CD patients with T1D, indicating an increase in intestinal permeability. Furthermore, these samples displayed the highest expression of forkhead box P3 (FoxP3) mRNA, a marker for regulatory T cells, as compared with other patient groups. At the same time, serum levels of IgA antibodies specific for the CD-related antigens deamidated gliadin and tissue transglutaminase (tTG) were the highest in CD patients with T1D. In contrast, no significant differences were found in IgA or IgG antibodies specific for bovine beta-lactoglobulin or Bifidobacterium adolescentis DSM 20083-derived proteins. There were also no differences in the transamidating activity of serum autoantibodies between patients and control individuals. Our results show that patients with T1D and newly detected CD exhibit severely altered intestinal permeability, strong local immune activation and increased immunoregulatory mechanisms in the small bowel. Further study is required to determine whether these extreme changes in this CD subgroup are due to some specific environmental factors (virus infections), unknown genetic effects or autoimmune reactions to antigenic targets in intracellular tight junctions.     

Ménétrier's disease associated with Kaposi's sarcoma

Ménétrier's Disease is a giant fold gastropathy whose precise etiology has remained enigmatic. However, mucosal changes characteristic of Ménétrier's Disease have been linked to diverse pathologies, both infectious and malignant. Here, we describe a novel association: Ménétrier's mucosa developing on top of underlying Kaposi's Sarcoma. Two male patients, ages 24 and 31, with HIV/AIDS underwent gastric biopsies that demonstrated Kaposi's Sarcoma. When the former patient expired, a more complete postmortem histologic examination of his stomach was undertaken. For each patient, endoscopic findings at the time of biopsy revealed thickened gastric mucosa overlying the Kaposi's changes. Microscopically, this thickened mucosa comprised hyperplastic foveolar cells that extended to the muscularis mucosa, characteristic of Ménétrier's mucosa. In both cases, special stains confirmed this impression. Dissection of the 24 year-old patient's stomach at autopsy demonstrated that the Ménétrier's mucosa was limited to areas where there was underlying Kaposi's Sarcoma, and that this mucosa was not present when the underlying stroma was normal. Our findings indicate, therefore, an association between Ménétrier's mucosal changes and Kaposi's Sarcoma; such an association has not, to our knowledge, been described previously in the literature.